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腹泻性大肠杆菌质粒多表位疫苗的设计:免疫信息学方法。

The design of multiepitope vaccines from plasmids of diarrheagenic Escherichia coli against diarrhoea infection: Immunoinformatics approach.

机构信息

Discipline of Chemical Engineering, University of KwaZulu-Natal, Howard Campus, Durban 4041, South Africa.

Department of Chemistry, Faculty of Natural and Agricultural Sciences, University of the Free State, Bloemfontein, South Africa; Department of Industrial Chemistry, Federal University, Oye, Ekiti, Nigeria.

出版信息

Infect Genet Evol. 2021 Jul;91:104803. doi: 10.1016/j.meegid.2021.104803. Epub 2021 Mar 5.

Abstract

Diarrhoea infection is a major global health public problem and is caused by many organisms including diarrheagenic Escherichia coli pathotypes. The common problem with diarrhoea is the drug resistance of pathogenic bacteria, the most promising alternative means of preventing drug resistance is vaccination. However, there has not been any significant success in the prevention of diarrhoea caused by E. coli through vaccination. Epitope-based vaccine is gaining more attention due to its safety and specificity. Sequence variation of protective antigens of the pathogen has posed a new challenge in the development of epitope-based vaccines against the infection, leading to the necessity of multiepitope based design. In this study, immunoinformatics tools were used to design multiepitope vaccine candidates from plasmid genome sequences of multiple pathotypes of E. coli species involved in diarrhoea infections. The ability of the identified epitopes to be used as a cross-protect multiepitope vaccine was achieved by identifying conserved, immunogenic and antigenic peptides that can elicit CD4 T-cell, CD8 T-cell and B-cell and bind to MHC I and II HLA alleles. The molecular docking results of T-cell epitopes showed their well binding affinity to receptive protein and with a wider population coverage. The different multiepitope-based vaccines (MEVCs) candidates were constructed and based on the types of epitope linker they contained. The MEVCs exhibited very good binding interactions with the human immune receptor. Among multiepitope vaccines constructed, MEVC6, MEVCA and MEVCB are more promising as potential vaccine candidates for cross-protection against gastrointestinal infections according to the computational study. It is also hoped that after validation and testing, the predicted multiepitope-based vaccine candidates will probably resolve the challenge of immunological heterogeneity facing enteric vaccine development.

摘要

腹泻感染是一个主要的全球公共卫生问题,由包括致泻性大肠杆菌病原型在内的多种病原体引起。腹泻的常见问题是病原菌的耐药性,预防耐药性最有希望的替代方法是接种疫苗。然而,通过疫苗接种预防大肠杆菌引起的腹泻尚未取得任何显著成功。基于表位的疫苗因其安全性和特异性而受到越来越多的关注。病原体保护性抗原的序列变异给基于表位的疫苗的开发带来了新的挑战,导致有必要进行多表位设计。在这项研究中,使用免疫信息学工具从涉及腹泻感染的多种大肠杆菌病原型的质粒基因组序列中设计多表位疫苗候选物。通过鉴定保守、免疫原性和抗原性肽,这些鉴定的表位能够作为交叉保护多表位疫苗使用,这些肽能够引发 CD4 T 细胞、CD8 T 细胞和 B 细胞,并与 MHC I 和 II HLA 等位基因结合。T 细胞表位的分子对接结果表明,它们与受体蛋白具有良好的结合亲和力,并具有更广泛的人群覆盖率。根据表位接头的类型,构建了不同的多表位疫苗候选物(MEVCs)。MEVCs 与人免疫受体表现出非常好的结合相互作用。在所构建的多表位疫苗中,MEVC6、MEVCA 和 MEVCB 根据计算研究更有希望成为针对胃肠道感染的交叉保护的潜在疫苗候选物。人们还希望,经过验证和测试后,预测的多表位疫苗候选物可能会解决肠道疫苗开发所面临的免疫异质性挑战。

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